"Central dogma of molecular biology"

Date:
1970
Reference:
PP/CRI/I/1/25
Catalogue details

Licence: In copyright

Credit: "Central dogma of molecular biology". Source: Wellcome Collection.

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    (Reprinted from Nature, Vol. 22T, No. 5258, pp. 561-563, August 8, 1970) Central Dogma of Molecular Biology y The central dogma of molecular biology deals with the detailed FRANCIS CRICK residue-by-residue transfer of sequential information. It states MRC Laboratory of Molecular Biology, that such information cannot be transferred from protein to either Hills Road, protein or nucleic acid. Cambridge CB2 2QH r The central dogma, enunciated by Crick in 1958 and the keystone of molecular biology ever since, is likely to prove a considerable over-simplification. Thìs quotation is taken from the beginning of an unsigned article 1 headed. Central dogma reversed, recounting the vei;y important work of Dr Howard Temin 2 and others 3 showing that an RNA tumour virus can use viral RNA as a template for DNA synthesis. This is not the first time that the idea of the central dogma has been mis understood, in one way or' another. In this article I explain why the term was originally introduced, its true meaning, and state why I think that, properly under stood, it is still an idea of fundamental importance. The central dogma was put forward 4 at a period when much of what we now know in molecular genetics was not established. All we had to work on were certain frag mentary experimental results, themselves often rather uncertain and confused, and a boundless optimism that the basic concepts involved were rather simple and probably much the same in all living things. In such a situation well constructed theories can play a really useful part in stating problems clearly and thus guiding experi ment. The two central concepts which had beon produced, originally without any explicit statement of the simplifica tion being introduced, were those of sequential information and of defined alphabets. Neither of th6se steps was trivial. Because it was abundantly clear by that time that a protein had a well defined three dimensional struc ture, and that its activity depended crucially on this structure, it was necessary to put the folding-up process on one side, and postulate that, by and large, the poly peptide chain folded itself up. This temporarily reduced the central problem from a three dimensional one to a one dimensional one. It was also necessary to argue that in spite of the miscellaneous list of amino-acids found in proteins (as then given in all biochemical text books) some of them, such as phosphoserine, were second ary modifications ; and that there was probably a universal set of twenty used throughout nature. In the same way minor modifications to the nucleic acid bases were ignored ; uracil in RNA was considered to be informationally PROTEIN analogous to thymine in DNA, thus giving four standard symbols for the components of nucleic acid. The principal problem could then be stated as the formulation of the general rules for information transfer from one polymer with a defined alphabet. to another. This could be compactly represented by the diagram of Fig. 1 (which was actually drawn at that time, though I am not sure that it was ever published) in which all possible simple transfers were represented by arrows. The arrows do not, of course, represent the flow of matter but the directional flow of detailed, residue-by-residue, sequence information from one polymer molecule to another. Now if all possible transfers commonly occurred it would have been almost impossible to construct useful theories. Nevertheless, such theories were part of our everyday discussions. This was because it was being tacitly assumed that certain transfers could not occur. It occurred to me that it. would be wise to state these preconceptions explicitly. O DNA // \ -PROTEIN RNA — O Fig. 2. The arrows show the situation as it seemed in 1958. Solid arrows represent probable transfers, dotted arrows possible transfers. The absent arrows (compare Fig. 1) represent the impossible transfers postulated by the central^dogma.^ They are the three possible arrows A little analysis showed that the transfer could be divided roughly into three groups. The first group was those for which some evidence, direct or indirect, seemed to exist. These are shown by the solid arrows in Fig. 2. They were: I (a) DNA—s-DNA I (&) DNA—>RNA I (c) RNA >Protein 1(d) RNA—î-RNA Fig. 1. The arrows show all the possible simple transfers between tl three families of polymers. They represent —¡j—' ■ detailed sequence informa The last of these transfers was presumed to ot of the existence of RNA viruses. Next there were two transfers (shown in Fig. 2 as dotted arrows) for which there was neither any experimental evidence nor any strong theoretical requirement. They II (a) RNA—>DNA (see the reference to Temin's work 2 ) II (6) DNA—s-Protein